title: Bioluminescent imaging of intracranial vestibular schwannoma xenografts in NOD/SCID mice.
abstract: OBJECTIVE
  Intracranial vestibular schwannoma xenografts can be successfully established and followed with bioluminescent imaging (BLI).
  
  
  BACKGROUND
  Transgenic and xenograft mouse models of vestibular schwannomas have been previously reported in the literature. However, none of these models replicate the intracranial location of these tumors to reflect the human disease. Additionally, traditional imaging methods (magnetic resonance imaging, computed tomography) for following tumor engraftment and growth are expensive and time consuming. BLI has been successfully used to longitudinally follow tumor treatment responses in a noninvasive manner. BLI's lower cost and labor demands make this a more feasible approach for tumor monitoring in studies involving large numbers of mice.
  
  
  METHODS
  Patient excised vestibular schwannomas were cultured and transduced with firefly luciferase expressing lentivirus. One million cells were stereotactically injected into the right caudate nucleus of 21 nonobese diabetic/severe combined immunodeficient mice. Schwannoma engraftment and growth was prospectively followed for 30 weeks after injection with BLI. After animal sacrifice, the presence of human tumor cells was confirmed with fluorescent in situ hybridization.
  
  
  RESULTS
  Eight (38%) of 21 mice successfully engrafted the schwannoma cells. All of these mice were generated from 4 (67%) of the 6 patient excised tumors. These 8 mice could be differentiated from the nonengrafted mice at 21 weeks. The engrafted group emitted BLI of greater than 100,000 photons/s (range, 142,478-3,106,300 photons/s; average, 618,740 photons/s), whereas the nonengrafted group were all under 100,000 photons/s (range, 0-76,010 photons/s; average, 10,737 photons/s) (p < 0.001). Fluorescent in situ hybridization analysis confirmed the presence of viable human schwannoma cells in much greater numbers in those mice with stable or growing tumors compared with those whose tumors regressed.
  
  
  CONCLUSIONS
  We have successfully established an intracranial schwannoma xenograft model that can be followed with noninvasive BLI. We hope to use this model for in vivo testing of schwannoma tumor therapies.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota 55905, USA. neff.brian@mayo.edu
authors.forename: Brian A
authors.initials: BA
authors.lastname: Neff
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Voss
authors.forename: Cory
authors.initials: C
authors.lastname: Allen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schroeder
authors.forename: Colin L W
authors.initials: CL
authors.lastname: Driscoll
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Link
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
authors.forename: Jann N
authors.initials: JN
authors.lastname: Sarkaria
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000601:surgery; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016086:Lentivirus / Q000302:isolation & purification; D008163:Luminescent Measurements / Q000379:methods; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009464:Neuroma, Acoustic / Q000473:pathology / Q000601:surgery* / Q000821:virology; D014183:Transplantation, Heterologous